Same Data, Two Submissions
If your clinical programme runs trials in both the European Union and the United States, you will submit essentially the same scientific data to two different regulatory agencies in two different formats with two different sets of expectations. The Investigational Medicinal Product Dossier (IMPD) goes to the relevant national competent authority (or centrally via CTIS) for EU clinical trial authorisation. The Investigational New Drug application (IND) goes to the FDA.
Both use the Common Technical Document (CTD) format as their structural framework. Both require a quality section covering drug substance and drug product. Both need non-clinical safety data and a clinical protocol. But the specific expectations within that structure differ in ways that matter when you are assembling the data package.
Key Differences: IMPD vs. IND
| Element | IND (FDA) | IMPD (EMA/National CAs) |
| Submission format | eCTD or non-eCTD electronic format to FDA | eCTD via CTIS for EU trials under CTR; national formats for legacy CTAs |
| CMC data expectation at Phase I | Fit-for-purpose; FDA responsive to first-cycle deficiencies; informal resolution common | Variable by national CA; some stricter than others; written clock-stop mechanism for major deficiencies |
| GMP certification requirement | US GMP (21 CFR 210/211) or equivalent; foreign facility inspection may be required | EU GMP certificate from relevant national CA or EMA required for all manufacturing sites |
| Impurity qualification thresholds | ICH Q3A/B thresholds; FDA may request additional qualification for specific impurities | Same ICH thresholds; EMA tends to be stricter on genotoxic impurity qualification at Phase I |
| Stability data required at filing | Data to cover duration of clinical study plus a buffer; real-time data preferred but extrapolation accepted | Similar expectations; some national CAs require more data at Phase I than FDA |
| Paediatric requirements | Paediatric Study Plan (PSP) under PREA for certain indications | Paediatric Investigation Plan (PIP) required earlier; may need agreed PIP before Phase III start |
| Expedited pathways | Fast Track, Breakthrough Therapy, RMAT for cell/gene therapies | PRIME for priority medicines; ATMP designation for cell/gene therapies |
Building One CMC Package That Serves Both
The most efficient approach to dual submissions is to build a single CMC data package that satisfies both agencies without creating parallel document sets. This is achievable because the CTD format was designed with harmonisation in mind. Module 3 content is structurally identical for an IND and an IMPD. The differences lie in the interpretation and the accompanying documents, not in the underlying data.
A CMC regulatory team with experience in both jurisdictions can write Module 3 sections that meet FDA expectations without creating gaps for EU national CAs, and vice versa. The key is knowing in advance where the expectations diverge, such as GMP certificate requirements or genotoxic impurity qualification, and addressing those areas proactively rather than reactively.
GMP Certificates: The Practical Difference That Trips People Up
This is the most common practical obstacle in dual submissions. The EU requires a GMP certificate from the relevant national competent authority for every manufacturing site listed in the IMPD. If your CDMO is based in the United States and does not hold an EU GMP certificate (issued following an EMA or national CA inspection), your IMPD cannot be accepted until that certificate is obtained or a mutual recognition agreement covers the site.
Ardena’s manufacturing facilities are inspected and certified under EU GMP by national competent authorities in Belgium, the Netherlands, and Spain. The US facility at Somerset, New Jersey operates under FDA cGMP. For programmes requiring dual submissions, the site selection decision should factor in the GMP certificate status of each facility before development work begins.
The CTIS Transition and What It Means for EU Submissions
Since January 2023, new clinical trial applications in the EU must be submitted through the Clinical Trials Information System (CTIS) under the EU Clinical Trials Regulation (CTR) 536/2014. CTIS centralises the submission and assessment process across EU member states, replacing the previous system of separate national submissions. The IMPD is submitted as part of the CTIS dossier, and the technical requirements for the quality section remain consistent with CTD Module 3 structure. EMA’s CTIS guidance provides detailed information on the transition.
How Ardena Supports Dual Submission Programmes
Ardena’s regulatory team has experience preparing CMC packages for both IND and IMPD submissions across its multi-site network. The team works with sponsors to identify divergent requirements early, structure the data generation plan to satisfy both agencies efficiently, and draft Module 3 sections that do not require significant rework between jurisdictions.
